Background: Cortical reorganization occurs in the adult central nervous system, especially during motor skill acquisition. This plasticity contributes to various forms of human behavior including skill learning and memory formation, consolidation, reconsolidation and short- and long-term retention. It is very important to understand the role of these different behavioral processes and of the mechanisms underlying these various forms of human plasticity during skill acquisition to improve skill learning and memory in healthy adults. Findings this year: The brain relies on consolidation processes to strengthen memories of motor skills acquired through training. Previously, consolidation has only been investigated over longer rest periods consisting of hour or days between training sessions. Over the past year, we developed a new line of inquiry that investigated consolidation processes over much shorter rest periods (on the order of several seconds) interspersed within a single training session. A group of healthy adults trained to acquire a novel motor skill inside of a magnetoencephalography (MEG) scanner that simultaneously recorded very fast changes in brain activity during training. We found that performance did not markedly change over short periods of practice. In contrast, performance improved significantly when subjects rested between practice periods, called offline learning, when subjects were at rest, and accounted almost all of the learning gains observed during the initial training session. These offline improvements were more pronounced in short rest periods between early training trials when the learning curve was steep. Using a machine learning approach, we were able to identify the neural signature that supported this type of fast learning. A future direction of this work will be to target this neural signature with non-invasive brain stimulation in an effort to enhance fast consolidation, which we expect to have important ramifications for the design of therapeutic interventions for neurological patients. Over the past year, we continued to advance an important research initiative aimed at characterizing intra- and inter-individual variability in responses to non-invasive brain stimulation. The rationale for this work is that a more complete understanding of how ongoing endogenous brain activity influences an individuals response to brain stimulation is crucial for the development of novel therapeutic interventions for rehabilitation of individual patients suffering from neurological injury or disease. Endogenous brain activity within sensorimotor networks is exhibits dynamic oscillations time-varying changes in phase (i.e. activity timing) and power (i.e activity magnitude). The influence of these dynamic oscillations on human motor function is unknown. We addressed this gap in knowledge by delivering transcranial magnetic stimulation (TMS) to the human motor cortex during simultaneous electroencephalography (EEG) recordings in a group of healthy adults. Motor evoked potentials (MEPs), a measure of communication strength between the brain and spinal cord important for generating movements, were categorized offline based upon sensorimotor rhythm phase and power when TMS was delivered. Our results showed that MEP amplitude could be predicted by an interaction between sensorimotor rhythm oscillatory phase and power. Communication strength between the brain and spinal cord was higher during sensorimotor rhythm troughs versus peaks when power was high while the opposite was true when power was low. In summary, our results show that timing of TMS delivery relative ongoing endogenous brain activity is an important factor in determining dosing and predicting responses to non-invasive brain stimulation in individuals. The ability to walk is a crucial motor function for daily life and is often impaired in patients suffering from neurological injury or disease. During the past year, we investigated the impact of non-invasive stimulation applied directly to the spinal cord (called transcutaneous spinal direct current stimulation or tsDCS) on treadmill training similar to what is currently standard in rehabilitation interventions for neurological patients with impaired walking ability. The goal of this randomized, sham-controlled and double-blind study was to determine if the addition of spinal cord stimulation enhanced learning during this training in healthy adults. Two groups of participants underwent a single backwards locomotion training (BLT) session on a reverse treadmill with simultaneously applied real or sham tsDCS. We found that real tsDCS applied in combination with training resulted in greater speed gains after 1 day, relative to sham tsDCS. Real stimulation also resulted in higher retention of these speed gains after one month. In summary, tsDCS improved both initial locomotor skill acquisition and long-term retention of the skill in healthy and suggest that this type of non-invasive stimulation may be a beneficial adjuvant therapy for standard treadmill training therapies used in rehabilitation settings for neurological patients. Finally, we expanded our work on memory encoding and consolidation over the past year to other memory domains affected by neurological injury or disease, as it has become increasingly apparent that motor impairments often occur in tandem with impairments to other memory systems. Working memory is the term used to describe our ability to select and temporarily hold information as needed for complex cognitive operations. The temporal and spatial brain activity that encodes and recalls this type of memory is not known. We investigated this issue by recording MEG data in a group of healthy adults while performing a working memory task. We once again used a machine learning analytical approach to decode memory features from the recorded brain activity, giving us insight into where and at what time this memory information is actively encoded within the brain. We showed that selection of the memory content relies on prefrontal and parieto-occipital persistent oscillatory neural activity. By contrast, reactivation of the memory content is encoded in a distributed occipitotemporal posterior network, preceding the working memory decision and in a different format than during the visual encoding. These results identified for the first time a neural signature of working memory content selection and reactivation. As a next step, we plan to use the features of this neural signature to devise a targeted non-invasive brain stimulation procedure aimed at enhancing working memory in healthy adults, and then applying the same approach to neurological patients suffering from memory disorders.